We have measured regional cerebral blood flow (rCBF) with oxygen-15 and positron emission tomography in young normal subjects during performance of a battery of frontal lobe tasks putatively involving working memory as well as during performance of matched sensorimotor control tasks for each frontal lobe task. The results indicate that the physiological concomitants of working memory in man include activation of the dorsolateral prefrontal cortex. Among the brain areas studied to date, this activation is localized to the inferior frontal gyrus in slices falling between six to eight centimeters above the canthomeatal line.